Tumor cells are characterized by a partial or complete loss of control of the cell cycle. This loss of cell cycle control results in excessive cell division activity and, thus, in uncontrolled growth. It is known that Plk1, the human orthologue of polo kinase of Drosophila, is an essential regulator of the M-phase of the cell cycle. Targeted interference with Plk1 function in cancer cells such as antisense molecules, siRNA, or antibody microinjection is known to result in mitotic arrest of the cells followed by the onset of cell death. Moreover, it was found that Plk1 is overexpressed in a wide variety of human cancers including, but not limited to breast, prostate, stomach or ovaries.
Inhibitors of Plk1 are known from WO 03/93249, WO 2004/014899, WO 2004/043936, WO 2004/074244, WO 2004/087652, WO 2005/019193, WO 2005/037827, WO 2005/042505, WO 2005/075470, WO 2005/123736, WO 2006/008028, WO 2006/018185, WO 2006/018222, WO 2006/021544, WO 2006/021547, WO 2006/025567, WO 2006/049339, WO 2007/030359, WO 2007/030361 and WO 2007/030366.
Insufficient susceptibility to known medicines of many tumor types requires the development of novel compounds as chemotherapeutic agents such as, for example, Plk1 inhibiting compounds interfering with cancer cell cycle and/or proliferation. Thus, subject of the present invention are novel Plk1 inhibitors.